N-acylamino acids are important starting products in peptide synthesis and intermediates for the production of biologically active agents. Moreover, N-acylamino acids are useful in detergents, drilling agent additives and food additives.
The manufacture of N-acylamino acids by acylation of corresponding amino acids with accumulation of salt by-products is known in the art. Regarding non-natural amino acids, the corresponding amino acid must frequently be manufactured in a number of stages. A single-stage process that avoids these disadvantages is the amidocarbonylation of aldehydes and amides, which is illustrated in the following diagram. ##STR3##
Amidocarbonylation was first described by Wakamatsu et al., (Chemical Communications 1971, page 1540 and in DE-A2-21 15 985). The carbonylation is performed in the presence of hydrogen gas with a 3:1 molar ratio of CO:H.sub.2. The cobalt carbonyl complex Co.sub.2 (CO).sub.8 is used as catalyst in a concentration of 30 mmol Co metal per litre of reaction mixture.
A further cobalt-catalysed process based on amidocarbonylation is described in GB 2 252 770. In this reaction the synthesis of N-acylamino acids is performed by reacting carboxylic acid amide with an aldehyde and CO in the presence of a metal catalyst and an acid co-catalyst.
EP-B-0 338 330 describes a process for the production of N-acylglycine derivatives with a catalyst system consisting of a palladium compound and an ionic halide. DE 195 45 641 and DE 196 29 717 describe a process for the preparation of N-acylglycine derivatives from a carboxylic acid amide and an aldehyde with palladium catalysis. In these reactions, ionic halides and additional acid may be used as co-catalysts.
DE 199 20 107.2 describes amidocarbonylation starting from nitrites in the presence of palladium or cobalt catalysts.
It is known from the literature that carboxylic acid amides react with aldehydes and carbon monoxide to N-acylamino acids. Until now only palladium and cobalt complexes have been used as catalysts for this reaction. Against this background it is surprising for the person skilled in the art that rhodium, iridium and ruthenium complexes also catalyze the reaction of amides with aldehydes and carbon monoxide. The reactions proceed with very high selectivities and good catalyst productivities. Unreacted educt can be readily recovered by recovery processes familiar to the person skilled in the art (distillation, crystallization) and can be reused, such that good yields can also be obtained in continuous processes.